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Suxiaojiuxin Pill Enhances Atherosclerotic Plaque Stability by Modulating the MMPs/TIMPs Balance in ApoE-deficient Mice

Zhang, Jinbao PhD*; Zhuang, Pengwei PhD*,†; Lu, Zhiqiang PhD*; Zhang, Mixia PhD*,†; Zhang, Teng PhD*; Zhang, Yanjun PhD*,†; Wang, Jinlei BS; Liu, Dan MS; Tong, Yongling BS

Journal of Cardiovascular Pharmacology: August 2014 - Volume 64 - Issue 2 - p 120–126
doi: 10.1097/FJC.0000000000000095
Original Article

Abstract: Suxiaojiuxin pill (SX) is a famous Chinese formulated product, which has been used to treat coronary heart disease and angina pectoris in China. This study was carried out to investigate the effect and possible mechanism of SX on the stability of atherosclerotic plaque in ApoE-deficient mice. ApoE−/− mice of 6–8 weeks old were fed with high-fat diet for developing artherosclerosis. After oral administration of SX for 8 weeks, histopathology of aortic plaque was performed by Sudan III and hematoxylin–eosin staining, and muscle protein was detected by Western blotting (WB). The mRNA and proteins associated with aortic plaque stability were detected by reverse transcription-polymerase chain reaction and WB, respectively. SX treatment could not only reduce serum triglyceride level and plaque area but also increase fibrous cap thickness and collagen content compared with the model group. WB results showed that SX could increase α-smooth muscle actin, tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2 protein expression, whereas decrease matrix metalloproteinase 2 (MMP-2) and MMP-9 protein expression. Moreover, SX could upregulate the expression of α-smooth muscle actin mRNA and downregulate the expression of vascular endothelial growth factor mRNA. These results showed that SX could enhance atherosclerotic plaque stability in ApoE-deficient mice. The mechanism may be associated with modulating the MMPs/TIMPs balance.

*Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin, China;

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; and

The Sixth Chinese Drugs Factory of Tianjin Zhongxin Pharmaceutical Co., Ltd., Tianjin, China.

Reprints: Yanjun Zhang, PhD, Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, No. 312 Anshanxi Road, Nankai District, Tianjin 300193, China (e-mail: zyjsunye@163.com).

Supported by the National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” (2012ZX09101202).

The authors report no conflicts of interest.

Received January 19, 2014

Accepted February 27, 2014

© 2014 by Lippincott Williams & Wilkins.